A 25-year-old woman with type 1 diabetes began producing her own insulin less than three months after receiving a transplant of reprogrammed stem cells. She is the first person with this condition to be treated using cells extracted from her own body.
“I can eat sugar now,” said the woman, who lives in Tianjin, China. It has been over a year since her transplant. She added, “I enjoy eating everything — especially hotpot.” The woman chose to remain anonymous for privacy reasons.
James Shapiro, a transplant surgeon and researcher at the University of Alberta, called the results of the surgery stunning. “They’ve completely reversed diabetes in the patient, who required substantial insulin before.”
The study, published in Cell, follows another trial in Shanghai, China. In April, researchers reported successfully transplanting insulin-producing islets into a 59-year-old man with type 2 diabetes. These islets were also derived from reprogrammed stem cells taken from his own body. He has since stopped taking insulin.
These studies are part of a few pioneering trials using stem cells to treat diabetes, which affects nearly half a billion people globally. Most have type 2 diabetes, where the body doesn’t produce enough insulin or cannot use it effectively. In type 1 diabetes, the immune system attacks the islet cells in the pancreas.
Islet transplants can treat diabetes, but there aren’t enough donors to meet demand. Recipients often need immune-suppressing drugs to prevent rejection of donor tissue.
Stem cells can grow any tissue in the body and can be cultured indefinitely, potentially offering a limitless source of pancreatic tissue. Using a patient’s own cells may also eliminate the need for immunosuppressants.
In a first-of-its-kind trial, Deng Hongkui and his team at Peking University extracted cells from three individuals with type 1 diabetes. They reverted these cells to a pluripotent state, allowing them to become any cell type. This reprogramming technique, developed by Shinya Yamanaka nearly two decades ago, was modified by Deng’s team. They used small molecules instead of proteins to trigger gene expression, giving them more control.
The researchers then generated 3D clusters of islets from these chemically induced pluripotent stem (iPS) cells. They tested the safety and effectiveness of these cells in mice and non-human primates.
In June 2023, the team injected about 1.5 million islets into the woman’s abdominal muscles. This new site for islet transplants allows better monitoring of the cells using MRI and makes removal easier if needed.
Two and a half months later, the woman was producing enough insulin to live without additional supplements. She has maintained this production for over a year and no longer experiences dangerous blood glucose spikes and drops, staying within the target range for over 98% of the day. “That’s remarkable,” said Daisuke Yabe, a diabetes researcher. “If this applies to other patients, it will be wonderful.”
While the results are intriguing, they need replication in more patients, says Jay Skyler, an endocrinologist. He wants to see if the woman’s cells continue producing insulin for up to five years before considering her “cured.”
Deng noted that results for the other two participants are also very positive. They will reach the one-year mark in November, and Deng hopes to expand the trial to include another 10 to 20 individuals.
Since the woman was already on immunosuppressants from a previous liver transplant, the researchers could not assess whether the iPS cells reduced rejection risk. In type 1 diabetes, there’s still a chance that the body could attack the islets due to the autoimmune condition. Deng noted that they didn’t see this reaction in the woman because she was on immunosuppressants, but they aim to develop cells that can avoid autoimmune responses.
While using a patient’s own cells has advantages, scaling up these procedures is challenging. Several groups have begun trials using islet cells created from donor stem cells.
Preliminary results from a trial by Vertex Pharmaceuticals reported that a dozen participants with type 1 diabetes received islets derived from donated embryonic stem cells. These were injected into the liver, and all participants began producing insulin when glucose was present in the bloodstream. Some became insulin-independent.
Last year, Vertex started another trial using islet cells from donated stem cells placed in a protective device. This device was transplanted into a person with type 1 diabetes, who did not receive immunosuppressants. That trial is ongoing.
Yabe is also preparing a trial using islet cells made from donor iPS cells. He plans to create sheets of islets and surgically place them in three patients with type 1 diabetes, who will receive immunosuppressants. The first participant is expected to receive their transplant early next year.
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